Comparative immunogenicity of recombinant B domain-deleted porcine factor VII and Hyate:C in hemophilia A mice presensitized to human factor VIII

Hyate is a commercial plasma-derived porcine factor (F)VIII concentrate that is Used in the treatment of patients with inhibitory antibodies to FVIII. OBI-l is a recombinant B domain-deleted form of porcine FVIII that is in clinical development for the same indication. Hemophilia A mice were presensitized with human FVIII to simulate clinical inhibitory antibody formation and then were randomized to receive OBI-l or Hyate:C in a comparative immunogenicity trial. OBI-l or Hyate:C were given in a series of four intravenous injections at weekly intervals at doses of 1, 10, or 100 U kg(-1). Inhibitory antibodies to porcine FVIII were not detected by Bethesda assay in most of the mice given OBI-1 or Hyate:C at doses of 1 or 10 U kg(-1), but were identified in 81% and 94% of mice given 100 U kg(-1) of OBI-l or Hyate:C, respectively. There was no significant difference between OBI-l and Hyate:C in inhibitory antibody formation at any dose, although there was a trend toward a lower Bethesda titer in OBI-l-treated mice at 10 U kg(-1) (P = 0.09). Total anti-FVIII antibodies to Hyate:C and OBI-l were also measured by ELISA using immobilized purified plasma-derived porcine FVIII and OBI-l, respectively. as antigens. At the 10 and 100 U kg(-1) doses, the mean anti-FVIII response was higher in Hyate:C-treated-mice than in OBI-l-treated mice (P = 0.02 and P = 0.004, respectively). The results using this model suggest that OBI-l may be less immunogenic and safer than Hyate:C in FVIII inhibitor patients.